Home Node/Aorta and Node/Liver SUV Ratios from18 F-FDG PET/CT May Improve the Detection of Occult Mediastinal Lymph Node Metastases in Patients with Non-Small Cell Lung Carcinoma
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Node/Aorta and Node/Liver SUV Ratios from18 F-FDG PET/CT May Improve the Detection of Occult Mediastinal Lymph Node Metastases in Patients with Non-Small Cell Lung Carcinoma

Rationale and Objectives

Research suggests that the semiquantitative determination of nodal 18 F–fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/computed tomography (CT) may be useful for the assessment of mediastinal metastases in patients with non-small-cell lung carcinoma (NSCLC). The aim of this study was to evaluate the diagnostic ability of using different standardized uptake value (SUV) parameters in the detection of ipsilateral mediastinal (N2) disease.

Materials and Methods

A total of 102 patients newly diagnosed with non-small-cell lung carcinoma who underwent 18 F-FDG PET/CT before surgery and had not received prior therapy were retrospectively included. All patients underwent surgical resection of the primary tumor and mediastinal lymph node dissection. On a station-based analysis, different SUV parameters (eg, mediastinal lymph node SUV, node/aorta SUV ratio, and node/liver SUV ratio) were evaluated using the histopathologic results as the reference standard. The optimal cutoff value for each SUV parameter was determined with receiver-operating characteristic curve analysis.

Results

The areas under the receiver-operating characteristic curves were 0.674, 0.693, and 0.715 for node SUV, node/aorta SUV ratio, and node/liver SUV ratio, respectively ( P < .05). With cutoff values of 3.15, 1.37, and 1.02 for node SUV, node/aorta SUV ratio, and node/liver SUV ratio, respectively, the sensitivity of 18 F-FDG PET/CT for N2 staging was 57.1%, 85.7%, and 71.4%, and specificity was 74.2%, 50.5%, and 61.9%.

Conclusions

Compared to node SUV alone, the use of node/aorta and node/liver SUV ratios resulted in improved detection of N2 metastases. The two SUV parameters may potentially improve the diagnostic accuracy of 18 F-FDG PET/CT for the diagnosis of N2 disease in patients with non-small-cell lung carcinoma.

Lung cancer is the leading cause of cancer-related mortality in women and men throughout the world . Of note, the 5-year survival rate for patients with stage II to IV disease is generally poorer than with other solid tumors . Approximately 25% of patients with non-small-cell lung cancer (NSCLC) were diagnosed after the cancer had spread to regional lymph nodes or beyond the primary site, while 51% were diagnosed after the cancer had already metastasized (distant stage) . In the absence of distant metastases, the metastatic spread to the ipsilateral mediastinal lymph nodes (defined N2 disease) is of paramount importance in determining both treatment and survival. Patients with NSCLC without pathologic evidence of N2 disease are generally treated with surgery, either with or without adjuvant therapy. In contrast, the 2010 National Comprehensive Cancer Network clinical practice guidelines for NSCLC recommend the use of definite concurrent chemoradiation therapy or induction chemotherapy with or without radiotherapy in N2-positive patients .

Research suggests that positron emission tomography (PET) with 18 F–fluorodeoxyglucose (FDG) is superior to other imaging modalities for staging lymph nodes and detecting distant metastases in patients with NSCLC . The high negative predictive value of 18 F-FDG PET reported in previous studies makes this technique a very useful means of replacing tissue biopsy for the diagnosis of regional lymph node metastases (ie, “metabolic biopsy”) . This may in turn avoid futile mediastinoscopy in patients with NSCLC. Unfortunately, 18 F-FDG PET alone seems insufficient to exclude N2 disease, because of the potential occurrence of false-negative findings by visual interpretation alone . The sensitivity of 18 F-FDG PET or 18 F-FDG PET/computed tomography (CT) for detecting N2 metastasis ranges from 40% to 90%, while the specificity ranges from 55% to 95% . In addition, 18 F-FDG PET may erroneously suggests the existence of mediastinal lymph node metastases in the presence of inflammatory changes. For these reasons, 18 F-FDG PET may either overestimate or underestimate the extent of the disease within the mediastinum in patients with NSCLC.

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Materials and methods

Patients

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18 F-FDG PET/CT

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Image Analysis

Visual interpretation

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Determination of SUV parameters

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Surgery

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Histopathology

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Statistical Analysis

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Results

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Table 1

Patient Characteristics ( n = 102)

Characteristic Value Men/women 56/46 Age (y) 34–81 (63.1) Histopathologic type Adenocarcinoma 74 Squamous cell carcinoma 14 Other 14 Lobe Right upper 28 Right middle 7 Right lower 27 Left upper 24 Left lower 16 Pathologic N stage ∗ N0 65 N1 18 N2 19

Data are expressed as numbers or as range (mean).

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Figure 1, Receiver-operating characteristic (ROC) curves of the semiquantitative approaches of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography for mediastinal N2 staging in patients with non-small-cell lung cancer. (a) ROC curve for node standardized uptake value (SUV), with area under the curve (AUC) of 0.674; (b) ROC curve for node/aorta SUV ratio, with AUC of 0.693; and (c) ROC curve for node/liver SUV ratio, with AUC of 0.715.

Figure 2, Fluorine-18–fluorodeoxyglucose (FDG) positron emission tomographic/computed tomographic image of a 68-year-old man with moderately differentiated adenocarcinoma in the left upper lobe. The N2 lymph nodes were free of metastasis on pathologic examination. There was slightly increased FDG uptake in the subcarinal station, with a node standardized uptake value (SUV) of 3.1 (7 mm in short-axis diameter), which was below the threshold of 3.15 (true-negative). The node/aorta and node/liver SUV ratios were 1.82 and 1.04, both above the cutoffs of 1.37 and 1.02 (false-positives).

Figure 3, Fluorine-18-fluorodeoxyglucose positron emission tomographic/computed tomographic image of a 63-year-old man with moderately differentiated adenocarcinoma in the right upper lobe and N2 metastasis proven in the subcarinal lymph node station, 8 mm in short-axis diameter. The node standardized uptake value (SUV) was 2.59 (below the threshold of 3.15, false-negative) but the node/aorta and node/liver SUV ratios were 1.55 and 1.16, above the thresholds of 1.37 and 1.02 (true-positives).

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Table 2

Characteristics of the Nine False-negative Lymph Node Stations on 18 F-FDG PET/CT Using Node SUV Criterion (3.15)

Station Lobe Histology Size of Metastatic Focus (mm) Node SUV Node/Aorta SUV Ratio Node/Liver SUV Ratio 2 RUL AD 10 × 6 2.00 0.92 0.74 3 RLL SCC 10 × 6, 6 × 4 2.27 1.55 ∗ 1.16 † 3 RUL AD 5 × 2, 1.5 × 1 2.51 0.92 0.88 3 RLL SCC 15 × 10 (all necrosis) 2.25 1.53 ∗ 1.00 4 RUL AD 14 × 18 2.87 1.65 ∗ 1.03 † 7 RLL AD 3 × 2.5 × 2.4 1.79 0.96 0.83 7 RLL LEC 4.7 × 4 × 3.7 1.60 1.39 ∗ 0.96 7 RUL AD 9 × 7, 8 × 5, 1 × 1 2.59 1.47 ∗ 1.12 † 9 RLL AD 2.1 × 1.3 × 1.2 1.91 1.38 ∗ 0.79

AD, adenocarcinoma; CT, computed tomography; FDG, fluorodeoxyglucose; LEC, lymphoepithelioma-like carcinoma; PET, positron emission tomography; RLL, right lower lobe; RUL, right upper lobe; SCC, squamous cell carcinoma; SUV, standardized uptake value.

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Table 3

Patient-based Diagnostic Performance of 18 F-FDG PET/CT for N2 Staging of Patients with NSCLC

Imaging Criteria Sensitivity Specificity Node SUV (cutoff 3.15) 68.4% (13/19) 75.9% (63 ∗ /83) Node/aorta SUV ratio (cutoff 1.37) 89.5% (17/19) 60.2% (50/83) Node/liver SUV ratio (cutoff 1.02) 84.2% (16/19) 66.3% (55/83) Visual interpretation 52.6% (10/19) 79.5% (66/83)

CT, computed tomography; FDG, fluorodeoxyglucose; NSCLC, non-small-cell lung cancer; PET, positron emission tomography; SUV, standardized uptake value.

Patient numbers leading to the sensitivity and specificity of each imaging criteria are shown in parentheses.

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Figure 4, Fluorine-18–fluorodeoxyglucose (FDG) positron emission tomographic/computed tomographic image of a 70-year-old man with moderately differentiated adenocarcinoma in the left upper lobe and no pathologic evidence of nodal metastasis. This subaortic lymph node was enlarged (11 mm in short-axis diameter) but was classified as negative for metastasis by visual interpretation (true-negative) considering the symmetric FDG uptake in the bilateral mediastinal and hilar areas, which suggested their benign inflammatory nature rather than metastasis. Using the node standardized uptake value (SUV) and the node/aorta and node/liver SUV ratios (4.06, 2.96, and 1.87, respectively, all above the cutoffs) would have resulted in a false-positive diagnosis for N2 disease.

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Discussion

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Conclusions

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