Home Clinical Significance of Combined Assessment of the Maximum Standardized Uptake Value of F-18 FDG PET with Nodal Size in the Diagnosis of Cervical Lymph Node Metastasis of Oral Squamous Cell Carcinoma
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Clinical Significance of Combined Assessment of the Maximum Standardized Uptake Value of F-18 FDG PET with Nodal Size in the Diagnosis of Cervical Lymph Node Metastasis of Oral Squamous Cell Carcinoma

Rationale and Objectives

This study aimed to elucidate the diagnostic accuracy of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) for nodal involvement in oral squamous cell carcinoma (OSCC), and to reveal clinically useful factors to distinguish between true-positive (TP) and false-positive (FP) nodes.

Materials and Methods

Thirty-eight patients with primary OSCC who underwent neck dissection were assessed. The diagnostic accuracy of F-18 FDG PET/CT was evaluated, and then compared with that of CT/ultrasonography (US). Furthermore, the association of the maximum standardized uptake value (SUVmax) and nodal size with the histopathologic findings was examined.

Results

Sensitivity and specificity using F-18 FDG PET/CT were 77.1% and 97.3%, and those using CT/US were 72.9% and 98.9%, respectively. The SUVmax of TP nodes was significantly higher than that of FP nodes. Nodes with SUVmax >4.5 were pathologically confirmed as metastasis. Nodes with SUVmax ≤4.5 were further discriminated between TP and FP nodes by using the long axis diameters or the ratios of long to short axis diameter as clinical parameters. Positive correlation between the SUVmax and the short-axis diameter was found in TP nodes. The AUC obtained from the ROC curves of the SUVmax alone (AUC, 0.804) was improved by combination with the long-axis diameter (AUC, 0.867) or the short-axis diameter (AUC, 0.846), although no significant difference was found.

Conclusions

These results indicated that F-18 FDG PET/CT was potentially useful in diagnosing preoperative nodal state. Furthermore, combined assessment of SUVmax with nodal size could be significant in the identification of metastatic lymph nodes in OSCC patients.

Cervical lymph node metastasis is one of the most significant prognostic factors for patients with oral squamous cell carcinoma (OSCC) . Accurate nodal staging is thus essential to determine an appropriate treatment. Preoperative nodal status is usually evaluated by means of clinical examinations, such as palpation, computed tomography (CT), ultrasonography (US), and magnetic resonance imaging (MRI). The diagnosis of cervical lymph node metastasis by CT and MRI is based on morphologic changes, such as nodal size and the contrast-enhancement pattern . US findings related to nodal metastasis are also dependent on changes in nodal size and internal heterogeneous echogenicity . However, findings obtained by these modalities do not always accurately reflect the presence of malignancy, because they are not specific for metastatic lymph nodes. Therefore, it is preferable to diagnose metastatic lymph nodes using a combination of these conventional methods with a novel modality that can detect the metabolic activity of cancer cells.

F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) is a functional imaging technique that detects malignant tumor by assessing activated glucose metabolism in cancer cells . There are growing evidences that F-18 FDG PET is a reliable imaging tool for the evaluation of patients with malignancies. In the head and neck region, F-18 FDG PET scanning has been mainly used for the screening of distant metastasis or unknown primary tumors . Recent reports have suggested that F-18 FDG PET is also useful to evaluate the primary tumor and nodal involvement in OSCC . Furthermore, most of these reports have concluded that F-18 FDG PET had higher specificity, with calculated specificities ranging from 62.2% to 100%, and that it was superior to conventional modalities in the assessment of cervical lymph metastasis . However, the specificity of this modality is hampered by the nonspecific accumulation of F-18 FDG in enlarged inflammatory lymph nodes. Therefore, the establishment of criteria to distinguish between true-positive (TP) nodes and false-positive (FP) nodes by F-18 FDG PET is needed.

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Materials and methods

Patients

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Table 1

Patient Characteristics

Cases Gender Age Primary Tumor Site Clinical Stage Local Recurrence Secondary Metastasis Neck Dissection Procedure for Neck Dissection Number of Dissected Lymph Nodes Number of Metastatic Lymph Nodes 1 M 22 Tongue II + - Bilateral RND (RS, levels I-V)

MRND (LS, levels I-V) 40 2 2 M 39 Gingiva IV - - Unilateral MRND (levels I-V) 17 0 3 M 42 Tongue II + Unilateral MRND (levels I-V) 16 1 4 M 43 Gingiva IV - - Unilateral SMND (level I) 6 0 5 M 50 Tongue II - - Unilateral SMND (level I) 8 0 6 M 50 Tongue III - + Bilateral RND (RS, levels I-V)

SMND (LS, level I) 27 2 7 M 51 Gingiva IV - - Unilateral RND (levels I-V) 8 1 8 M 52 Tongue IV - - Unilateral RND (levels I-V) 18 1 9 M 53 Tongue IV - - Unilateral RND (levels I-V) 14 8 10 M 54 Tongue II - - Unilateral SMND (level I) 7 0 11 M 60 Floor of the mouth II - - Unilateral SMND (level I) 4 0 12 M 61 Tongue II - - Unilateral RND (levels I-V) 13 1 13 M 61 Tongue IV - - Unilateral MRND (levels I-V) 15 2 14 M 62 Tongue IV - - Unilateral RND (levels I-V) 18 0 15 M 63 Tongue II - - Unilateral RND (levels I-V) 11 1 16 M 64 Floor of the mouth IV - + Bilateral SMND (RS, level I)

RND (LS, level I-V) 21 1 17 M 67 Gingiva II - - Unilateral SMND (level I) 6 0 18 M 67 Gingiva IV + - Unilateral MRND (levels I-V) 25 0 19 M 67 Gingiva IV - - Bilateral SMND (RS, level I)

SMND (LS, level I) 17 0 20 M 67 Floor of the mouth II - - Bilateral SMND (RS, level I)

SMND (LS, level I) 8 1 21 M 69 Gingiva IV - - Bilateral SMND (RS, level I)

SMND (LS, level I) 16 0 22 M 69 Floor of the mouth IV - - Bilateral RND (RS, levels I-V)

MRND (LS, levels I-V) 22 2 23 M 70 Floor of the mouth IV - - Bilateral SMND (RS, level I)

SMND (LS, level I) 8 0 24 M 71 Gingiva IV - - Unilateral SMND (level I) 4 0 25 M 76 Gingiva III + Unilateral MRND (levels I-V) 9 1 26 M 77 Gingiva IV - - Unilateral SMND (level I) 8 0 27 M 81 Buccal mucosa III - - Unilateral SMND (level I) 6 1 28 M 83 Floor of the mouth IV - + Bilateral SMND (RS, level I)

MRND (LS, level I-V) 22 5 29 F 34 Tongue III - - Unilateral MRND (levels I-V) 20 2 30 F 63 Tongue III - - Unilateral RND (levels I-V) 21 4 31 F 65 Tongue II - - Unilateral SMND (level I) 5 0 32 F 70 Tongue II - - Unilateral SMND (level I) 12 0 33 F 70 Tongue II - + Unilateral RND (levels I-V) 9 1 34 F 76 Gingiva IV - - Bilateral SMND (RS, level I)

SMND (LS, level I) 7 2 35 F 80 Tongue II - + Unilateral RND (levels I-V) 12 6 36 F 87 Gingiva II - + Unilateral RND (levels I-V) 3 1 37 F 87 Gingiva IV - - Unilateral SMND (level I) 5 1 38 F 89 Gingiva I - + Unilateral SMND (level I) 10 1

LS, left side; MRND, modified RND (dissection levels I-V with preservation of the internal jugular vein and/or spinal accessory nerve); RND, radical neck dissection; RS, right side; SMND, submandibular neck dissection (dissection level I).

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CT Imaging

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Table 2

Diagnostic Criteria for Cervical Lymph Node Metastasis Using CT/US

Modality Criteria for Metastasis Criteria for Non-metastasis CT 1. Rim enhancement or heterogeneous enhancement pattern

2. Short-axis diameter ≥10 mm (when lymph node has central necrosis) None B-mode US 1. Presence of echogenicity

2. Short axis diameter ≥10 mm (when lymph node has neither echogenicity nor hilar echoes) 1. Presence of hilar echoes

2. L/S ratio ≥3.5 (when the lymph node has neither echogenicity nor hilar echoes) Power Doppler US 1. Peripheral vascularity

2. Aberrant multi-focal vascularity

3. Nonvascularity in lymph node measuring 8 mm or more in short-axis diameter Hilar vascularity in lymph node measuring 6 mm or more in short-axis diameter

CT, computed tomography; US, ultrasonography.

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US

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F-18 FDG PET/CT

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Histopathologic Examination

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Statistical Analyses

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Results

Assessment of Cervical Lymph Node Metastasis Using F-18 FDG PET/CT or Contrast-enhanced CT/US

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Figure 1, Truly positive nodal findings using computed tomography and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in an 89-year-old female with squamous cell carcinoma of the right lower gingiva. (a) Contrast-enhanced computed tomography scan shows a mass ( arrow ) with heterogeneous enhancement in the right submental region ( b : axial, c : coronal). PET finds F-18 FDG uptake ( arrow ) in the right submental region. (d) Metastasis was histopathologically confirmed in this node (bar = 200 μm).

Table 3

Diagnostic Accuracy of CT/US and PET Examination in 38 Patients (498 Nodes)

Imaging Modality TP FP FN TN Sensitivity (%) Specificity (%) Accuracy (%) PPV (%) NPV (%) CT/US 35 5 13 445 72.9 98.9 96.4 87.5 97.2 [ 18 F]-FDG PET 37 12 11 438 77.1 97.3 95.4 75.5 97.6P value ∗ .724 .146 .424 .183 .837

FN, false negative; FP, false positive; NPV, negative predictive value; TN, true negative; TP, true positive; PPV, positive predictive value.

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Diagnostic Differences between TP and FP Nodes Using F-18 FDG PET/CT

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Figure 2, Comparison of the maximum standardized uptake value (SUVmax) between true-positive (TP) and false-positive (FP) nodes in F-18 fluorodeoxyglucose positron emission tomography/computed tomography. Each point represents a lymph node. The average of the SUVmax in TP nodes was significantly higher than that in the FP nodes (6.5 ± 3.1 vs. 3.4 ± 0.6, * P < .01).

Figure 3, Comparisons of the long-axis diameter (a) , short-axis diameter (b) and long to short axis (L/S) ratio (c) between the true-positive (TP) and false-positive (FP) nodes with maximum standardized uptake value (SUVmax) ≤4.5 in F-18 fluorodeoxyglucose positron emission tomography/computed tomography. Each point represents a lymph node. In terms of the long-axis diameters and the L/S ratio, TP nodes were significantly longer than FP nodes (16.0 ± 6.2 vs. 11.1 ± 2.6 mm, * P < .05; 2.0 ± 0.8 vs. 1.4 ± 0.3, * P < .05). No significant difference between TP and FP nodes was seen in the short-axis diameters (8.7 ± 3.1 vs. 7.8 ± 1.5 mm).

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Correlation between the SUVmax and Size of the Metastatic Lymph Nodes

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Figure 4, Association of the maximum standardized uptake value (SUVmax) with the long-axis diameter (a) and the short-axis diameter (b) . The lymph nodes with a high SUVmax (>4.5) were pathologically confirmed as being metastatic, even though their sizes were small (≤10 mm in long-axis diameter or <5 mm in short-axis diameter). Strong positive correlation between the SUVmax and the short-axis diameter were found by the Spearman rank-correlation coefficient (ρ = 0.5129, P = .0012), although no significant correlation was seen between the SUVmax and the long-axis diameter (ρ = 0.2445, P = .1447).

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ROC Analyses

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Figure 5, Receiver operating characteristic curves and area under the curve (AUC) of the maximum standardized uptake value (SUVmax) (a) , combinations of the SUVmax with the long-axis diameter (b) and with the short-axis diameter (c) . The AUC of the SUVmax alone (AUC, 0.804) was improved by combination with the long-axis diameter (AUC, 0.867) or the short-axis diameter (AUC, 0.846), although no significant difference was seen (d) . Results were compared by the two-tailed test ( P < .05 was considered to be significant).

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Discussion

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