Jurnal ENT

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Original article

Prospective comparison of18

F-FDG PETwith conventional imaging modalities (CT, MRI, US)

in lymph node staging of head and neck cancer

Stefan Adams1, Richard P Baum1, Tankred Stuckensen2, Klaus Bitter2, Gustav Hör1

1 Department of Nuclear Medicine, Johann Wolfgang Goethe University Medical Center, Frankfurt/Main, Germany2 Department of Oral and Maxillofacial Surgery, Johann Wolfgang Goethe University Medical Center, Frankfurt/Main, Germany

& misc :Received 17 February and in revised form 12 June 1998

& p.1:Abstract. The aims of this study were to investigate thedetection of cervical lymph node metastases of head andneck cancer by positron emission tomographic (PET)imaging with fluorine-18 fluorodeoxyglucose (FDG)and to perform a prospective comparison with computedtomography (CT), magnetic resonance imaging (MRI),sonographic and histopathological findings. Sixty pa-tients with histologically proven squamous cell carcino-ma were studied by PET imaging before surgery. Preop-erative endoscopy (including biopsy), CT, MRI and so-nography of the cervical region were performed in allpatients within 2 weeks preceding 18F-FDG whole-bodyPET. FDG PET images were analysed visually and

quantitatively for objective assessment of regional traceruptake. Histopathology of the resected neck specimensrevealed a total of 1284 lymph nodes, 117 of whichshowed metastatic involvement. Based on histopatholog-ical findings, FDG PET correctly identified lymph nodemetastases with a sensitivity of 90% and a specificity of 94% (P


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European Journal of Nuclear Medicine Vol. 25, No. 9, September 1998

tomography (CT), magnetic resonance imaging (MRI),sonography] have been applied for the localization of primary head and neck tumours, regional lymph nodemetastases and their relationship to adjoining anatomicalstructures [11]. Discrimination between reactive enlarge-

ment of lymph nodes and tumour-infiltrated nodes on thebasis of morphological criteria may be problematic [12].

Fluorine-18 fluorodeoxyglucose (18F-FDG) is amarker of tumour viability, based upon the increasedglycolysis that is associated with malignancy as com-pared with most normal tissues. It has also been suggest-ed that tumours with increased FDG uptake appear moreaggressive and are associated with a less favourableprognosis [13]. Head and neck carcinomas have highglycolytic activity and increased FDG uptake [14, 15].

The aims of this study were to evaluate the detectionof regional lymph node metastases of head and neck cancer by 18F-FDG PET and to perform a prospective

comparison with CT, MRI, sonographic and histopatho-logical findings.

Materials and methods

Patients. & p.2:The study group consisted of 60 patients (16 female and

44 males; mean age 58.3±10 years, range 38–76 years) with histo-

logically proven squamous cell carcinoma of the head and neck

region, all scheduled for surgery. Physical examination was per-

formed by the head and neck surgeon. Preoperative endoscopy

(including biopsy) was performed in all patients within 2 weeks

preceding 18F-FDG whole-body PET. Informed consent was ob-

tained from all patients.

Histopathological examination. & p.2:All resected tissues were exactly

localized and documented at each level to allow correlation be-

tween histopathological findings and preoperative imaging results.

Classification of the primary tumour and regional lymph node me-

tastases was based on the TNM system of the International Union

Against Cancer (UICC 1992). The primary tumours were differen-

tiated into four groups (G1 well differentiated–G4 anaplastic), as

described by Hermanek and Sobin [16].

PET technique. & p.2:PET studies were acquired on an ECAT Exact 47

whole-body tomograph (Siemens-CTI, Knoxville, Tenn., USA)

with a transaxial field of view of 16.2 cm (slice thickness 3.4 mm;

spatial resolution 4 mm). Prior to the18

F-FDG PET, patients hadbeen fasting for at least 12 h. Patients with known diabetes melli-

tus were excluded from the study, so normal glucose plasma levels

(2.0)

were considered malignant. However, the final decision to classify

a focus as a metastasis was based on the visual evaluation, which

also took into account the history of the patient (e.g. inflammation

in the head and neck region). Results were coded according to the

TNM classification by two experienced nuclear medicine physi-

cians (in independent, blinded evaluations) on the screen displayof a work station (three-dimensional black-and-white as well as

colour images) utilizing the original data set. Scans were docu-

mented as color printouts and on X-ray films (laser technique).

Conventional imaging modalities. & p.2:High-resolution ultrasound

studies (7.5 MHz, linear array, Volu-Son 530 D, Kretz, Marl, Ger-

many) of the regional lymph nodes were performed in all patients

within 2 weeks preceding 18F-FDG whole-body PET.

CT scans of the cervical region were obtained in all patients

within 1 week preceding the PET examination with a conventional

CT scanner (Somatom Plus, Siemens, Erlangen, Germany). Slice

thickness was 4–5 mm (continuously, without a gap). Contrast

material enhancement was achieved by intravenous administration

of 100 ml of non-ionic contrast material (Ultravist 300, Schering,Berlin, Germany) with a power injector rate of 0.5 ml/sec.

Concerning MRI studies (Siemens Magnetom Vision, Erlan-

gen, Germany), we first obtained non-enhanced transversal slices

with an inversion recovery (T2-weighted slices) with a slice thick-

ness of 6.0 mm (gap 0.6 mm). In addition, coronal slices (T1-

weighted) were performed with a slice thickness of 6.0 mm and

with a gap of 1.5 mm. All patients had transversal T1-weighted

slices before and after intravenous administration of contrast me-

dium [0.1 mmol of gadolinium diethylenetriamine penta-acetic

acid (Gd-DTPA)/kg body weight; slice thickness 6.0 mm, gap

0.9 mm].

Results of conventional imaging were classified preoperatively

according to the TNM classification by two experienced radiolo-

gists without any knowledge of the background of the patients.Regional lymph nodes of the head and neck region more than

12 mm in diameter were considered pathological. In addition,

lymph nodes were also staged as tumour involved if other signs of

malignancy, such as grouping of nodes, central necrosis, shape

(e.g. spherical lymph nodes) or pathological contrast material en-

hancement were encountered.

Statistical analysis. & p.2:Values are given as mean ±SD. The sensitivi-

ty, specificity, positive predictive value, negative predictive value

and accuracy for the imaging modalities were calculated using

standard statistical formulas. Student’s t -test and Spearman corre-

lation were used to examine the correlation between continuous

variables in the groups, and non-continuous variables were com-

pared with a chi-square test. Statistical significance was assumedwhen P≤0.05.

Results

Among the 60 patients, 15 primary tumours were local-ized in the tongue, 28 in the floor of the mouth, 5 in thepalate and 12 in the mandibular or maxillary region(Fig. 1). All patients underwent surgery; 22 had T1, 15T2, 3 T3 and 20 T4 tumours. Concerning the postopera-tive grading, 15 primary squamous cell carcinomas were

G1, 30 G2 and 15 G3 (Fig. 2). FDG PET identified theprimary lesions in 59 cases. In one patient with a small

Mean PET counts ( Ci/ml Calibration factorInjected dose (MBq)/Body weight (g)

µ ×.


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and well-differentiated squamous cell carcinoma (T1)PET failed to detect the primary tumour.

FDG uptake was calculated for each primary lesion inthe attenuation-corrected regional bed position of the

head and neck region. The SUVBW ranged from 2.5 to13.8, with a mean of 4.54±2.8. The comparison of glu-cose plasma levels and FDG uptake in primary lesionsrevealed no statistically significant correlation(P = 0.42). Furthermore, there was no statistically signif-

icant relationship between primary tumour uptake of FDG and tumour grade (P = 0.9). Interestingly, therewas a tendency towards higher SUVBW values in lymphnode metastases in patients with increased FDG uptakein primary lesions (P = 0.04).

In our study 1284 lymph nodes were resected anddocumented according to level. The preoperative lymphnode staging according to the TNM classification wascompared with postoperative histopathological findings.Twenty-nine patients revealed no malignant lymph nodeinvolvement (N0), whereas 31 patients demonstrated 117lymph node metastases. There were ten patients with on-ly one ipsilateral lymph node metastasis of less than

3.0 cm in diameter (N1) (Fig. 3). In 18 patients multipleipsilateral malignant lymph nodes (N2b) were diagnosedand three patients demonstrated bilateral lymph node in-volvement (N2c). Based on histopathological findingsFDG PET correctly identified lymph node metastaseswith a sensitivity of 90% and a specificity of 94%(P1.5 cm, central necrosis, sphericalnode& /fig.c :


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80%, respectively (P


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and neck cancer CT is still the gold standard, althoughMRI is gaining in importance [25]. However, in ourstudy MRI (specificity 79%) was not better than CT(specificity 85%) in distinguishing between malignantand inflamed tissues. If strict criteria of morphological

imaging are applied (size >1.5 cm, central necrosis,grouping nodes, spherical shape) CT has been shown toalter N staging in 20%–30% of the examined patients[26]. It should be noted that more than 40% of all lymphnode metastases are localized in nodes smaller than1.0 cm in diameter [27, 28]. In comparison with theseresults, in the present study the smallest lymph node me-tastasis detected by CT was only 1 cm in diameter,whereas FDG PET was able to localize smaller lymphnode metastases (0.6 cm in diameter).

In patients with malignant regional lymph node in-volvement, radical neck dissection is usually performedin order to eradicate the cervical metastatic foci. Correct

N staging is necessary to define the appropriate surgicaltreatment because radical neck dissection affects both thefunction and the appearance of patients. Concerninglymph node staging, both CT and MRI correctly stagedabout 50% of our patients when compared with histo-pathological findings, whereas metabolic imaging withFDG PET revealed no malignant lymph node involve-ment in 23 of 29 patients (79%). In this study, FDG PETdetected lymph node metastases with a sensitivity of 90%and a specificity of 94%, respectively. Similar resultsconcerning sensitivity and specificity for the detection of lymph node metastases have been reported by Lauben-bacher et al. [29]. It is important to emphasize that in-creased FDG uptake is also observed in benign lymphnodes and peritumoral granulation tissue as a result of in-flammatory reaction (activated macrophages) [30].

In agreement with findings of other groups, our studypopulation showed an inhomogeneous FDG uptake inprimary tumours (SUVBW: 2.5–13.8) and lymph nodemetastases (SUVBW: 2–11) [15, 29, 31]. Possible expla-nations of this heterogeneity may be the mixture of cellclones in tumours, different expression of the glucosetransporter gene/glycolysis-related genes or changes in-duced by oncogenic alteration [32, 33]. The use of othersubstances labelled with positron emitters such as L-

[11

CH3]-methionine and L-1-[11

C]-tyrosine seems to bemore suitable in the evaluation of patients with palpablelymph nodes given their potential to differentiate be-tween malignant and inflammatory tissue [34–36].However, L-[11CH3]-methionine shows bilateral symmet-rical accumulation in the salivary glands; therefore tu-mour detection in these regions and especially at thesubmandibular and submental lymph node levels may beproblematic [37].

In patients with advanced head and neck tumours,Valk et al. demonstrated the potential cost-effectivenessof an FDG PET-based strategy by avoiding surgery fornon-resectable tumours. The savings from contraindicat-

ed surgical procedures exceeded the cost of PET imag-ing by ratios of 2:1 to 4:1, depending on the indication

[38]. In the current health care environment, imagingmodalities must not only change medical managementbut also demonstrate that those changes improve patientoutcome. However, additional studies are necessary toshow the potential effect of FDG PET on the manage-

ment of patients with head and neck cancer.In conclusion, this prospective, histopathologically

controlled study confirms FDG PET as the procedurewith the highest sensitivity and specificity for detectinglymph node metastases of head and neck cancer, and thishas become a routine method in our University MedicalCenter. Furthermore, the optimal diagnostic modalitymay be a fusion image showing the increased metabo-lism of the tumour and the anatomical localization.

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