British Journal of Oral and Maxillofacial Surgery (2005) 43, 1—6

EDUCATION SECTION

Positron emission tomography in cancer

of the head and neck
Sharon F. Hain∗

The Institute of Nuclear Medicine, Middlesex Hospital, UCH NHS Trust and Charing Cross Hospital,
Hammersmith Hospitals NHS Trust, London W1T 3AA, UK

Accepted 10 September 2004

Available online 5 November 2004

KEYWORDS Summary The use of positron emission tomography (PET) has increased in oncol-
Squamous cell ogy and in the assessment of head and neck tumours, where it is most useful for
carcinoma; recurrent disease. It has good sensitivity and specificity for diagnosis and staging
FDG; but is generally not necessary except in difficult cases. Quantitative measures of
PET;
uptake on PET at diagnosis and after treatment do seem to have prognostic value
independent of other information about the tumour and so PET may influence man-
Head and neck cancer
agement. It also has a role in the identification of an unknown primary site and
of synchronous primaries and metastases (often missed by other imaging). Fusion
imaging with magnetic resonance (MRI) or computed tomography (CT) adds a new
dimension with improved value for each technique.
© 2004 The British Association of Oral and Maxillofacial Surgeons. Published by
Elsevier Ltd. All rights reserved.

Introduction
The use of 18-fluorodeoxyglucose (FDG) PET has
grown rapidly in oncology. It is a metabolic imaging
tool that provides information beyond the anatomi-
cal constraints of conventional imaging. It is partic-
ularly helpful in the areas where conventional imag-
ing has difficulties, including when previous treat-
ment prevents the separation of recurrence from
changes resulting from treatment. It can establish
whether enlarged lymph nodes contain tumour or
are reactive, and it can detect small foci of disease
* Tel.: +44 20 73809426; fax: +44 20 76370578.
E-mail address: s.hain@nucmed.ucl.ac.uk.
and assess the whole body in one step with a much
lower dose of radiation than whole body CT.
The main tracer used in PET is FDG, which is
a glucose analogue that enters cells through the
glucose transport proteins (GLUT1—6). Once inside
the cells it is phosphorylated to GDG-6-phosphate
but does not proceed further down the biochemi-
cal pathway. As cancer cells have a higher glycolytic
rate the tumour cells take up the FDG more actively
than normal cells. The radioactive label fluorine-18
emits positrons at the site of tumour and these un-
dergo an annihilation reaction with electrons, emit-
ting two gamma rays at 180◦ to each other. With a
ring camera placed around the patient these events
are detected and the data are reconstructed to give
high quality images.

0266-4356/$ — see front matter © 2004 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.bjoms.2004.09.006
2 S.F. Hain
Primary tumours
Assessment of primary tumours before
treatment
The treatment of primary squamous cell carcinoma
of the head and neck is dependent on staging of
the tumour. Detection of extension into adjacent
tissues and structures is important and is done by
the conventional anatomical imaging techniques
of CT and MRI. For this they will always have a
place and they are highly sensitive for primary dis-
ease (67—88%) but do lack specificity (50—75%). In
comparison, FDG-PET has an equivalent sensitiv-
ity (71—95%) but is more specific (67—100%).1—4 In
most cases, an FDG-PET is not necessary, but in the
rare cases where doubt exists about the diagnosis or
extension of disease — for example, into the cranial
vault — it may be useful. This is particularly true as
the PET and CT or MRI can be fused to allow com-
bined anatomical and metabolic imaging in these
difficult cases.
Because of the metabolic nature of PET, it has
been suggested that it can provide prognostic infor-
mation. Minn et al. suggested that high uptake of
FDG was correlated with advanced disease.5 More
recently, Halfpenny et al. found that the standard
uptake value (a semi-quantitative marker of up-
take) provided prognostic information independent
of stage and diameter of the tumour.6 An uptake
value greater than 10 was an important marker for
poor outcome and could identify those patients who
require intensive treatment.
Regional lymph node status
When lymph nodes are involved survival is dramat-
ically reduced and treatment must change. Clinical
palpation is inaccurate with false negative rates of
5—44%, and false positive rates of 13—25%.7—9 With
conventional imaging, the sensitivity for detection
of lymph node involvement ranges from 36 to 95%
and the specificity from 58 to 97%.10—15 The diag-
nosis of involved nodes on CT or MRI is based on
size, generally using a cut off of 1 cm to differenti-
ate benign from malignant disease. The problem is
that large or multiple lymph nodes may simply be
reacting to the underlying process and small nodes
may contain cancer cells. Indeed more than 40% of
metastases have been found in lymph nodes smaller
than 1 cm.16 These are missed with conventional
imaging. As PET is a metabolic tool, it can define
disease in small nodes and exclude it in large nodes.
There have been many studies on this, and overall
the data shows that FDG-PET is both more sensi-
tive (70—100%) and more specific (84—100%) than
conventional imaging.10—15 One drawback of PET is
that false positives can be found in infected nodes
and PET can also fail to detect small numbers of
cancer cells.
The patient with clinically N0 neck is a spe-
cial case, as 70% of these could potentially avoid
the morbidity of neck dissection or radiotherapy.
This is one area where PET was expected to be of
some value, but this is controversial. Stoeckli et al.
found PET to have such poor sensitivity and speci-
ficity that it had no role in the clinically N0 neck.17
Sentinel lymph node biopsy is more reliable.17,18
Like all imaging methods, PET has a limit of de-
tection and therefore micrometastatic disease can
be missed. An alternative view was presented by
Hollenbeak et al. who studied the cost effective-
ness in N0 necks of proceeding from CT to PET.19
They found that the incremental cost-effectiveness
of this strategy was $8718 per life year saved or
$2505 per quality adjusted life year and concluded
that in N0 necks PET is cost effective.
Synchronous primary and distant
metastases
As many as 10% of patients with a primary SCC of
the head and neck may have a second primary in
the head and neck and about 1% may have a pri-
mary in a lung. These, as well as distant metastases,
have important implications for management. Sev-
eral small studies have suggested that PET may
be of use.20—22 Synchronous primaries have been
found in 1—12% of patients, and distant metastases
in 12—21%. Whole body PET is capable of finding
these extra lesions20,21 and causes less radiation
than multiple cavity CT. Wax et al. showed that PET
was significantly more accurate in identification of
synchronous primaries than bronchoscopy.22 In all
studies many of the lesions identified on PET were
not seen on any other imaging and so the PET di-
rectly altered management (Fig. 1).
About 22% of patients develop a second primary
within 5 years. PET may be the best way of moni-
toring this, but there are no studies in this area as
yet.
Management changes at staging
In many tumours such as lymphomas and lung
cancers, PET has been found to both upstage and
downstage the disease at diagnosis, and this has im-
portant implications for management.23,24 In head
and neck cancer it also provides additional informa-
tion in up to 22%.25 In about half of these there is a
Positron emission tomography
Figure 1. A coronal FDG-PET in a patient with a laryngeal
SCC. PET identified uptake in the right lung which was
found to be a synchronous primary.
direct and appropriate change in management as a
result of this additional information.
Recurrence and response to treatment
Assessment and recurrence
The assessment of patients after treatment of can-
cer of the head and neck is more difficult than as-
sessment before treatment. Most importantly, the
treatment itself, whether by operation, radiother-
apy, or chemotherapy, all lead to distortion of the
anatomy, which can interfere with the clinical and
radiological assessment of the region. In attempting
to assess recurrence, biopsy of the treated region
can lead to complications, including progressive
necrosis at a site of incipient radiation necrosis.26
Blind biopsy may easily fail to find any disease al-
3
Figure 2. A patient treated 1 year previously by ra-
diotherapy for carcinoma of the larynx presented with
hoarse voice and discomfort in the neck. Biopsy speci-
men showed no cancer and conventional imaging showed
changes resulting from treatment with no definite evi-
dence of recurrence. A sagittal FDG-PET through the left
side of the neck showed increased uptake (arrow) indica-
tive of recurrent tumour, which proved to be true.
though it is present. These problems may be solved
by metabolic imaging (Fig. 2).
There are now many studies that have examined
the place of FDG-PET in the diagnosis of recurrent
disease. The sensitivity for detecting recurrence at
the primary site is 80—100% with a specificity of
61—81%.26—32 This is a clear improvement over con-
ventional imaging. Obviously, PET does not show the
anatomy clearly and, particularly when a salvage
operation is planned, combining CT or MRI with PET
can be valuable to the surgeon (Fig. 3). The newer
PET/CT machines can do this automatically. It is,
however, possible with PET and MRI used separately
by the use of readily available registration software
that can combine the two forms of imaging. This is
particularly valuable for identifying the site of re-
currence, which may be only a small area within a
large field of treatment and allows accurate plan-
ning of further treatment.
In requesting PET it is important that the refer-
rer understands its potential limitations and the im-
portance of an accurate history. After radiotherapy
the question of the timing of the PET is important.
Greven et al.29 showed that there were more false
negatives if the scan was done 1 month after com-
pletion of treatment compared with one done after
4 months. Notably though, at 1 month all positive
scans did reflect disease.
False positives can be the result of inflammation
in the primary site or nodes, and an accurate history
of any infection in the region is required to enable
accurate reporting.
4 S.F. Hain

Figure 3. A CT-PET in a 54-year-old man who had had a SCC of base of tongue 3 years previously, thought to be T3N2A,
treated by operation and radiotherapy. In the past 6 months he had complained of increasing pain in the right side of
the neck. He had several fine needle biopsies and MRIs, none of which showed recurrent disease. There was a strong
clinical suspicion of recurrence. The figure shows coronal images of CT (left), PET (middle) and colocalised study.
There is a rim of increased uptake on PET (full arrow) surrounding a mass on CT (white arrow). This indicates a rim of
active recurrence and necrotic centre probably explaining why the biopsy specimen showed no cancer. A further area
of uptake was seen on PET (dashed arrow) lying near the petrous temporal bone. Colocalisation with CT showed that
there was a previously unseen small mass here close to but not invading bone.

Response to treatment identifies the site of the tumour in about 40—60% of

In a study of 143 patients Wong et al. found that
PET and SUV (a semi-quantitative measure of up-
take) were independent predictors of relapse-free
and overall survival.32 An increase in SUV by one
unit increased the relative risk of relapse by 11%
and of death by 14%. Kunkel et al. in a study of
97 patients found that FDG uptake was a highly
accurate marker of disease and an increased up-
take predicted an increased risk of death.33 It
has a vital role in counselling and management of
patients.
Brun et al. scanned 47 patients 1 to 3 weeks
after radiotherapy with or without chemotherapy
and showed that FDG-PET reflected early response
and local control of the tumour, and survival af-
ter a median follow up of 3 years.34 As we men-
tioned earlier, some concern was raised by Greven
et al. about false negative studies at 1 month com-
pared to 4 months, so that 4 months may be a
more accurate time to assess progressive or residual
disease.29
Lowe et al. found that PET taken 1—2 weeks
after starting chemotherapy, showed large reduc-
tions in FDG uptake in patients who responded
completely.35
Special problems
The unknown primary
cases.36—39
Other tumours of the head and neck
Salivary gland tumours
PET is unable to differentiate sufficiently well be-
tween benign and malignant disease in salivary
glands. Benign lesions including Warthin tumour and
pleomorphic adenoma may have high uptake.40
PET is, however, valuable in thyroid cancer par-
ticularly in those patients who have increased con-
centrations of thyroglobulin but do not take up
radioiodine.41
Other tracers
Although FDG is useful there are some limitations
with FDG-PET, and other tracers are being explored.
It has become clear that degree of hypoxia in tu-
mours is an indicator of outcome and some studies
have been done with fluoromisonidazole that sug-
gest that this tracer may be used to predict re-
sponse to radiotherapy.42 More recently 11 C me-
thionine tyrosine (TYR) PET has been evaluated.
This tracer allows measurement of the rate of syn-
thesis of protein. Dynamic TYR PET is accurate for
evaluation of tumours after radiotherapy, with up
to 100% sensitivity and specificity for discrimina-
tion of tumour status compared with conventional
imaging.43 It has also provided early information af-
ter chemotherapy.44

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