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Combined PET/CT : Clinical Applications362
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PET-CT based Radiotherapy
Treatment Planning
R. Prabhakar and T. Ganesh
Treatment of cancer with radiation aims at eradication of the tumor while preserving
organ function and reducing radiation induced toxicity. This requires spatially accurate
visualization of tumorous tissues in relation to the surrounding healthy structures. Before
the advent of computed tomography (CT) scanner, clinicians used to target the tumor based
on clinical examination and radiographic imaging. Lack of ability to distinguish between
soft tissues and the fact that it is a superimposed two-dimensional (2-D) image of a threedimensional (3-D) volume are some of the major limitations of conventional radiographic
imaging. Further, quantitative analysis of the tumor volume is not possible in conventional
2-D imaging. All these limitations are overcome by CT imaging. Computed tomography
forms the primary imaging modality for image based radiotherapy treatment planning. With
the inclusion of many newer imaging modalities, each with unique diagnostic capabilities,
multi-modality imaging is the current buzzword in radiotherapy. Imaging modalities like
magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT),
ultrasound imaging and molecular imaging (PET) are being increasingly incorporated into
radiotherapy treatment planning. Additionally, treatment evaluation tools in radiotherapy
such as dose volume histogram (DVH), tumor control probability (TCP), normal tissue
complication probability (NTCP) and conformality index (CI) completely depend upon the
imaging modality used for treatment planning. Unlike CT or MRI, which shows anatomic
details, positron emission tomography (PET) images the biochemical or physiologic
phenomena. Because of this, PET offers substantial advantages in oncologic imaging.
The important steps involved in the management of cancer with radiotherapy are as
follows
1. Immobilization
36 8
PET-CT based Radiotherapy Treatment Planning 369
2. Imaging
3. Tumor localization
4. Treatment planning
5. Patient positioning
6. Treatment
7. Quality assurance and verification
Each and every step in the course of radiation therapy is of utmost importance and
discrepancy in anyone of these steps will have severe impact on the final treatment outcome.
Historically, treatment planning has gone through three phases based on the way the
tumor volume is delineated. The first phase might be called “targeting by surface anatomy”
which was used till the advent of the radiation simulator. This method consisted of placing
the patient on the treatment machine and drawing the radiation ports using surface anatomy
landmarks, the physical landmarks, the physical examination and radiographic studies as a
guide. The dose is calculated to a few points. The advent of the radiation simulator changed
this paradigm. In the second phase, the radiation ports could be set up using radiographic
anatomy as a guide. All pertinent anatomical structures, critical organs and the tumor itself
had to be drawn onto a single slice usually transverse, central plane, giving this approach its
traditional name of 2-D planning with display of 2-D dose distribution. In this method, the
dose distribution can only be evaluated on the central plane, without the capability of
assessing dose distributions for situations of axially varying tumor and normal tissue anatomy,
altered beam parameter, blocks etc. The third historical phase of treatment planning could
be called a tumor-based approach. Here the tumor is identified on the fully 3D radiographic
study, usually CT and the radiation beams are shaped around it. Three-dimensional planning
should incorporate the following four major functions in three dimensions.
1. Define anatomical configuration and relationship of the tumor and all relevant normal
tissues;
2. Design and alter the radiation beam parameters;
3. Rapidly calculate the resultant dose distribution and
4. Analyze a plan and compare alternative plans.
With the introduction of advanced radiotherapy treatment techniques like 3-D conformal
radiotherapy (3-D CRT) and intensity modulated radiotherapy (IMRT), it has become utmost
important to delineate the target volume precisely in order to achieve a good tumor control.
One of the fundamental prerequisites for 3-D conformal radiotherapy is the accurate
localization of the target. Radiotherapy treatment planning requires delineation of two different
types of volumes for planning.
PET-CT based Radiotherapy Treatment Planning370
● The target volumes
● The organs at risk (OAR)
The International Commission on Radiation Units and Measurements (ICRU) has defined
several volumes needed for radiotherapy treatment planning in its report 50 (1). The volumes
defined are as follows.
● Gross tumor volume (GTV)
● Clinical target volume (CTV)
● Planning target volume (PTV)
● Treated volume (TV)
● Irradiated volume (IV)
The GTV describes the tumor as visible from the image data. The CTV includes the
GTV and the sub-clinical microscopic extensions of the disease. As there are chances that
the CTV can be shifted due to patient movement during treatment, uncertainties in patient
repositioning and organ movement, ICRU has defined the concept of planning target volume
(PTV) to encompass these uncertainties to prevent the tumor being missed during treatment.
The tumor volume that is enclosed within the prescribed isodose is defined as the treated
volume. The irradiated volume comprises the whole volume that receives a considerably
higher dose than the tolerance of the surrounding normal tissue.
Organs at risk (OARs) are defined as tissues that show a higher radio-sensitivity than
normal tissue. Therefore they have to be particularly spared during treatment. Organs at risk
are delineated from the visible outline in the image data.
In 1999, ICRU published Report 62 as a supplement to its Report 50, with minor
modifications of the original concepts (1,2). It defined two margins in between CTV and
PTV. In order to account for the variations in size, shape, and position of the CTV in
relation to anatomical reference points (e.g., filling of stomach or bladder, movements due
to respiration, etc.) it defined the internal margin (IM). The setup margin (SM) is added to
take into account uncertainties in patient-beam positioning. These two margins reflected the
differences in the sources of uncertainties. The selection of beam size and arrangement is
based on the PTV.
The internal margin is mainly due to physiologic variations that are difficult or impossible
to control. In contrast, the setup margin is added because of uncertainties related mainly to
technical factors that can be reduced by more accurate set up and immobilization of the
patient, as well as improved mechanical stability of the machine.
Similarly, ICRU report 62 has added a margin for organs at risk to compensate for these
variation and uncertainties, which led to Planning Organ at Risk Volume (PRV). In order to
analyze various plans for a particular patient, ICRU defined the concept of a Conformity
PET-CT based Radiotherapy Treatment Planning 371
Index (CI) as the quotient of the treated volume and the volume of the PTV. This definition
of the CI implies that the treated volume totally encompasses the PTV.
As per the ICRU guidelines, the GTV is delineated on the treatment planning images
followed by CTV and then the PTV. Hence, accurate delineation of GTV is very essential as
it directly affects the PTV volume. In the infancy stage of radiotherapy, the treating physician
used to give a large margin around the GTV with square or rectangular radiation portals,
which encompasses a large amount of normal tissues, thus leading to more complications
and also restrictions in the total dose to the tumor volume. As the technology progressed
from a simple 2-D to advanced 3-D conformal radiotherapy, and in the current era of image
guided radiotherapy (IGRT), the CTV to PTV margin has been considerably reduced. Hence,
accurate delineation of tumor volume is very much essential and any miss in tumor volume
delineation will lead to tumor underdosage. The gross tumor volume can be reconstructed in
3-D from tomographic slices, taken in the tumor region, forming the basis for 3-D treatment
planning. As of now, CT is the best imaging modality for 3-D treatment planning as it
provides information about the tissue densities in the form of electron density which is
required for radiotherapy dose calculation. On the other hand, MRI is very often superior to
CT, especially for differentiating tumor tissue from healthy tissue. In addition to CT and
MRI, PET imaging has the potential to include information on tumor metabolism. Besides,
PET can add knowledge on different biological characteristics of the tumour itself and it
also gives information on differentiation between tumor recurrence and radiation necrosis.
This biological information might be used in the future to delineate a biological target
volume and to adapt radiotherapy treatment, both in terms of volume as well as in dose.
More basic research and clinical confirmation of these theoretical studies are awaited, before
the definite role of PET in radiation treatment planning becomes clear. PET provides
information about the physiology rather than anatomy. 18F-fluorodeoxyglucose (18F-FDG) is
the most common imaging agent used for imaging in PET. It is helpful in differentiating
malignant from benign growths, as well as in showing the spread of malignant tumors. PET
imaging can help detect recurrent brain tumors and tumors of the lung, colon, breast, lymph
nodes, skin, and other organs. For several treatment sites it has already been shown that PET
studies have a strong potential to improve staging, prognosis, therapy selection, treatment
planning, and follow-up. It is also used for slow growing tumors and hypoxic regions.
A major limitation of PET includes the fact that it is not absolutely specific for tumor,
and that false-positive findings can occur in inflammatory states. Another important drawback
is that the images are of substantially lower resolution than those of CT and MRI and
therefore PET is generally poor at delineating anatomic detail and difficulty in defining the
peripheries of the tumor. Since radiotherapy dose calculation requires accurate definition of
external body and normal structure surrounding the tumor volume, PET alone cannot be
used for radiotherapy treatment planning. To utilize PET in radiotherapy, it should be fused
either with CT or MRI. An integrated PET-CT or PET-MRI is the best option. PET-CT for
treatment planning of three-dimensional conformal radiation therapy improves the
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