Int. J. Radiation Oncology Biol. Phys., Vol. 71, No. 1, pp. 2–4, 2008Copyright � 2008 Elsevier Inc.

Printed in the USA. All rights reserved0360-3016/08/$–see front matter

doi:10.1016/j.ijrobp.2008.01.019

EDITORIAL

WHERE DO WE DRAW THE LINE? CONTOURING TUMORS ON POSITRON EMISSIONTOMOGRAPHY/COMPUTED TOMOGRAPHY

MICHAEL P. MACMANUS, M.D., M.R.C.P., F.R.C.R., F.F.R.R.C.S.I., F.R.A.N.Z.C.R.,*z

AND RODNEY J. HICKS, M.D., F.R.A.C.P.yz

*Department of Radiation Oncology and yCentre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne,Victoria, Australia; and zUniversity of Melbourne, Melbourne, Victoria, Australia

Positron emission tomography, Radiotherapy, Radiotherapy planning, Lung cancer.

Sane judgment abhors nothing so much as a pictureperpetrated with no technical knowledge, althoughwith plenty of care and diligence.

Albrecht Durer, The Art of Measurement (1525)

The human brain and eye have capacities unmatched by

any computer. In our everyday lives, we unthinkingly

perform tasks of astonishing visual complexity. When we

recognize the face of a politician from a few pen strokes in

a caricature or navigate a car through a maze of streets in

rush-hour traffic, we perceive the edges and shapes of things,

recognize the effects of movement, and perform complex

feats of visual pattern recognition. Human visual intelligence

forms the basis of the imaging disciplines. Without the com-

bination of visual ability, training, and knowledge provided

by the imaging specialist, complex and expensive medical

imaging technology is useless. It is possible to replace or ‘‘as-

sist’’ the human eye and brain in some aspects of image

interpretation by using automated processes. Although these

might eliminate the effects of observer variability, the value

of human skill and judgment should not be forgotten.

In conformal radiotherapy (RT) planning, the radiation

oncologist is required to identify tumor margins on a three-

dimensional imaging study, usually a computed tomography

(CT) scan, to define the gross tumor volume (GTV). The

GTV can then be used to derive the clinical target volume

and planning target volume. Poor planning target volume

definition can cause a geographic miss and treatment failure.

However, the information contained in a CT scan is often

inadequate for GTV delineation. For example, in non–

small-cell lung cancer (NSCLC), the boundary between

tumor and atelectasis, or the limit of invasion of soft tissues,

might be invisible. Lymph node staging is notoriously

Reprint requests to: Michael MacManus, M.D., M.R.C.P.,F.R.C.R., F.F.R.R.C.S.I., F.R.A.N.Z.C.R., Department of RadiationOncology, Peter MacCallum Cancer Institute, St. Andrew’s Place,East Melbourne, Vic 3002, Australia. Tel: (+61)3-9656-1111;

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inaccurate (1). Not surprisingly, when different physicians

use CT images to contour volumes for the same group of

NSCLC patients, wide variations occur (2). Radiation oncol-

ogists define widely different volumes from one another

(interobserver variability) and often contradict themselves

when recontouring the same case again (intraobserver

variability). Because CT scans contain insufficient informa-

tion, gaps are filled by guessing. People guess differently.

The use of a predefined protocol for tumor contouring can

increase consistency (3). Nevertheless, variability still occurs,

partly because the quality of visual information is poor.

Positron emission tomography (PET) has dramatically im-

proved the imaging of many common malignancies. Fluoro-

deoxyglucose (FDG) accumulation in tumor cells increases

the contrast between normal tissues and tumor deposits. Conse-

quently FDG-PET/CT images are often excellent for RT plan-

ning (4). The reproducibility of contouring is increased by the

use of PET/CT compared with CT alone, but it still can show

some variability when a visual (human) contouring method is

used. Tumor margins are indistinct on PET images because of

movement, partial volume effects, and the lower spatial resolu-

tion of PET. The lesion appearance is influenced by the quality

of the PET scanner, the reconstruction algorithm, and the image

display threshold. Without standardization, apparent variations

in tumor dimensions occur, making it difficult to ensure unifor-

mity of contouring among different clinicians and facilities.

Various automated quantitative algorithms have been

developed to define the margins of tumors objectively using

PET (5). The simplest methods use the standardized uptake

value (SUV) (6). Cancers typically have greater SUVs than

the blood pool. Often an arbitrary SUV level such as 2.5 or

3 is used to define the contour around a tumor. Some groups

have used an SUV contour derived from a percentage of the

Fax: (+61)3-9656-1424; E-mail: michael.macmanus@petermac.orgConflict of interest: none.Received Dec 12, 2007. Accepted for publication Jan 15, 2008.

Contouring tumors on PET/CT d M. P. MACMANUS AND R. J. HICKS 3

peak SUV. Such volumes can closely resemble the contours

drawn by a human observer, with the important difference

that automated contour placement is absolutely reproducible

provided the lesion has been correctly identified at the outset.

Does this mean that SUV-based approaches are necessarily

superior to human contouring of the GTV?

Unfortunately, things are not so simple. An SUV contour is

a single piece of information. Its exclusive use ignores all

other imaging and clinical information. Left to its own de-

vices, an SUV-based contouring algorithm would inappropri-

ately include nearby metabolically active noncancerous

regions within the GTV. These regions could include myocar-

dium, brown fat, and inflammatory lesions, easily recognized

as such by an experienced clinician. In practice, automated

contouring approaches are confined to physician-defined

regions of interest. Non-nuclear medicine clinicians might

inappropriately regard SUV as an absolute property of a tumor

and not a function of the biodistribution of tracer on a particu-

lar scanner on a particular occasion, influenced by the timing

of imaging after injection, the patient’s blood sugar level and

state of relaxation, their size and fat content, and the image

processing protocols used. True tumor size does not vary

with the technical details of an imaging study.

Many cancers have heterogeneous uptake of FDG. Simply

using an SUV contour for edge definition in a necrotic tumor

can exclude some tumor regions with a thin rim of peripheral

FDG uptake. Lesions with low SUV might not be contoured at

all, and small pathologically involved nodes could be ignored

because their measured SUV will be lower than their ‘‘true’’

SUV. An SUV cutoff that provides a satisfactory tumor–

lung boundary could mistake the boundary between tumor

and heart, liver, mediastinum, or chest wall. Use of an SUV

contour can either overestimate or underestimate the size of

the region in which the tumor moves, because of the combina-

tion of respiratory blurring of activity over a larger volume

than the true tumor occupies physically at any point in time

and temporal undersampling, respectively. Studies using

moving phantoms have produced no comprehensive solution

suitable for routine clinical use. For nongated RT, a ‘‘func-

tional’’ volume, which integrates both the structural volume

of metabolically active tumor cells and the temporal blurring

of this volume due to respiratory motion, actually reflects the

more appropriate GTV for RT planning than the volume

define by an instantaneous CT scan (7).

More complex tumor contouring methods have been ex-

plored. Because fixed threshold values, typically 40–50%

of the maximal lesion intensity, can be unreliable (8),

contrast-dependent, adaptive thresholding methods are being

investigated. Phantom studies with varying ‘‘lesion’’ and back-

ground activities have been conducted to derive the relation-

ship between the true volume of homogenously filled

‘‘lesions,’’ usually spherical, and the threshold to be applied

to the PET data. The ‘‘ideal’’ thresholds have been found to

vary according to the signal/background ratios. Use of a sig-

nal/background algorithm for FDG-PET has produced more

appropriate tumor volumes than CT or magnetic resonance im-

aging-based volumes in head and neck cancers compared with

pathologic specimens. In NSCLC, the use of a source/back-

ground ratio, edited by the observers, reduced the interobserver

variability and agreed with the limited pathologic analysis (9).

If we use these more advanced automated methods and

discard human visual contouring, how do we know when

the automated methods are doing a good job of defining

the GTV? In clinical practice, unlike in phantom studies,

no independent confirmation of the true position of the cir-

cumference of a moving tumor is possible during RT. There-

fore, when an automated method gives a result that looks

plausible, we accept it. When it does not, we can adjust the

parameters and try again or edit the automated contour man-

ually. What is the reference standard then? It is, for now, the

opinion of the treating radiation oncologist, who signs the

treatment prescription plan. We must ask ourselves, then,

how much has the automated method added when its goal

was to produce a result acceptable to a human observer?

Returning to the opening remarks in this editorial, humans

have remarkable visual abilities that allow them to integrate

many kinds of information. Perhaps reproducible GTV con-

tours can be produced visually using PET/CT. Fused PET/

CT scans contain much more information than CT scans alone

and provide a much better basis for human judgment. Prelim-

inary results from a study in which the GTV in patients with

NSCLC was contoured by different observers on fused

PET/CT scans suggested that the use of a fastidious contour-

ing protocol can promote excellent conformity, provided the

protocol is followed diligently (10). Automated contouring

should certainly continue to be explored, but as a tool to assist

human judgment, not a substitute for it. When using auto-

mated contouring in clinical practice, we must be aware of

its limitations and be prepared to edit the results. In clinical tri-

als in which PET-assisted treatment planning is included, the

target volumes should not simply be defined by the SUV. Suf-

ficient flexibility should be included to allow for the incorpo-

ration of other information. Fully automated contouring can

sometimes be 100% reproducible but 100% wrong.

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